Princeton Weekly Bulletin January 11, 1999
Genomic Analysis
Tilghman to head interdisciplinary institute for fundamental biological research
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A member of the National Academy of Sciences, the Institute of Medicine, and the Royal Society of London, Tilghman was one of the architects of the national effort to map the entire human genome.
The institute will be unique in applying the perspectives and analytical tools of fields such as physics, chemistry, computer science, mathematics and engineering -- fields that have experience in managing complexity and problems of integration -- to what Tilghman describes as an "avalanche of new information in genomics and structural biology that poses fundamentally new challenges for biologists."
Integration of information
According to Tilghman, "As we acquire all the information that will become available to us from the human genome project, improvements in technology and other initiatives, the challenge for the future lies in studying the principles that drive the integration of information in complex biological systems. The field of molecular biology has made enormous progress in the 20th century by reducing the complexity of living organisms to component parts. With complete genetic blueprints that will give us the identities of all biological molecules almost in hand, there is now an exciting opportunity to study how the component parts are assembled into the whole.
"Building on Princeton's traditional strengths in the sciences and engineering, we hope to create an environment where scientists of all stripes, from biology, physics, chemistry, mathematics and various fields of engineering, can work together to solve biological problems that depend on taking large amounts of information about genes, proteins or structures and revealing how they are integrated into a coherent whole. I am very excited about the prospect of helping to build such an institute."
Exceptional distinction
In announcing Tilghman's appointment, President Shapiro said, "I am very pleased that Shirley Tilghman has agreed to provide leadership for this unprecedented effort to bring together scientists from a range of disciplines to work on some of the most important, challenging and interesting problems in biology. She is herself a scientist of broad interests and exceptional distinction, with a proven capacity for identifying topics that dramatically change our understanding of the fields in which she works."
Said Provost Jeremiah Ostriker, who coordinated a review process to identify the best possible person to head the new institute, "After extensive conversations with some of the world's leading scientists in this field, we realized that our clear first choice was already on our own faculty. Professor Shirley Tilghman brings extraordinary credentials as a scholar, a teacher and a leader in her field, but she also brings such critically important personal qualities as creativity, breadth of interests, resourcefulness, imagination, determination and a rare ability not only to work well with others but to help others -- in a variety of fields and circumstances -- to do their best work."
Princeton since 1986
A native of Canada, Tilghman received her Honors BSc in chemistry from Queen's University in Kingston, Ontario, and after two years of secondary school teaching in Sierra Leone, West Africa, she earned her PhD in biochemistry from Temple University. During postdoctoral studies at the National Institutes of Health, she made a number of groundbreaking discoveries while participating in cloning the first mammalian gene, and then continued to make scientific breakthroughs in understanding the structure and mechanism of expression of mammalian genes during development as an independent investigator at the Institute for Cancer Research, Fox Chase.
In 1986 Tilghman moved to Princeton to become Prior Professor of the Life Sciences. In 1988, while remaining at Princeton, she also joined the Howard Hughes Medical Institute as an investigator. Her work broadened to include the analysis of genes whose expression pattern is determined by whether the gene is inherited from mothers or fathers, and she proposed the first model to explain the mechanism of parent-specific silencing of genes. Tilghman chairs Princeton's Council on Science and Technology, and in 1996 she received the President's Award for Distinguished Teaching. She recently received national attention for a report on "Trends in the Careers of Life Scientists," issued by a commission she chaired for the National Research Council.
Tilghman's interests in genome analysis stem from her participation in the National Research Council's committee that set the blueprint for the U.S. effort in the Human Genome Project, and she was one of the founding members of the National Advisory Council of the Human Genome Project Initiative for the National Institutes of Health.
Princeton's $900 million 250th Anniversary Campaign includes a goal of $60 million to support the work of this new institute. Of this goal, $40 million would be used to construct a new state-of-the-art building, and $20 million would help to create several new faculty positions and provide research and start-up funds for the institute.
Tilghman offers examples of topics the new institute might explore:
• The genes of all organisms are thought to have evolved from a small number of protein building blocks, probably less than 1,000. Those building blocks were selected in evolution because they fold into a structure with useful properties. A new field of chemistry is being born that is approaching function through structure.
• A single cell in a multicellular organism has on its surface upwards of 100 different proteins, each of which is there to receive external cues. How does a cell integrate all those signals, some of which may be sending contradictory messages? This problem requires the knowledge of scientists who are used to managing complex circuits. This problem multiplied billions of times is one way to represent information processing in the brain.
• Organisms as disparate as fruit flies and humans use the same genes to establish their body plans. Why do flies have wings and humans have arms? How do the same genetic circuits create such different outcomes? One aspect of this problem is the manner by which cells generate the force to move together in sheets, and how the extent and direction of the force is controlled. This is a problem in physics.
• What is the logic, if any, to the pattern in which the 80,000 genes are organized along the chromosome? Is there a pattern, some higher order structure within the cell nucleus, that facilitates the coordinate and integrated action of genes? The solution to this problem will require us to know the three-dimensional architecture of the nucleus, a problem in structural chemistry.
• How can we approach the study of biological processes that involve the action of many genes? We need new mathematical models for studying multigenic traits.